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Immunol."],"abstract":"<jats:p>C-reactive protein (CRP) is an established marker of rheumatoid arthritis (RA) but with ill-defined actions in the pathogenesis. Here, we show that CRP regulates the differentiation of osteoclasts, a central mediator of joint inflammation and bone erosion in RA, in a conformation- and receptor activator of NF-\u03baB ligand (RANKL)-dependent manner. CRP in the native conformation is ineffective, whereas the monomeric conformation (mCRP) actively modulates osteoclast differentiation through NF-\u03baB and phospholipase C signaling. Moreover, mCRP can bind RANKL, the major driver of osteoclast differentiation, and abrogate its activities. The binding and inhibition of RANKL are mediated by the cholesterol binding sequence (CBS) of mCRP. Corroborating the<jats:italic>in vitro<\/jats:italic>results, CRP knockout exacerbates LPS-induced bone resorption in mice. These results suggest that mCRP may be protective in joint inflammation by inhibiting pathological osteoclast differentiation and that the CBS peptide could be exploited as a potential RANKL inhibitor.<\/jats:p>","DOI":"10.3389\/fimmu.2018.00234","type":"journal-article","created":{"date-parts":[[2018,2,19]],"date-time":"2018-02-19T04:15:32Z","timestamp":1519013732000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Monomeric C-Reactive Protein Binds and Neutralizes Receptor Activator of NF-\u03baB Ligand-Induced Osteoclast 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